5-58494786-G-A

Variant names:

• chr5-58494786-G-A
• rs772963136
• NM_001304431.2:c.250G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001304431.2(GAPT):​c.250G>A​(p.Val84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V84L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GAPT NM_001304431.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 0 publications found

Genes affected

GAPT (HGNC:26588): (GRB2 binding adaptor protein, transmembrane) Predicted to be involved in B cell homeostasis and B cell proliferation involved in immune response. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049161404).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304431.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPT	NM_001304431.2	MANE Select	c.250G>A	p.Val84Ile	missense	Exon 3 of 3	NP_001291360.1	Q8N292
	GAPT	NM_001304428.2		c.250G>A	p.Val84Ile	missense	Exon 3 of 3	NP_001291357.1	Q8N292
	GAPT	NM_001304429.2		c.250G>A	p.Val84Ile	missense	Exon 3 of 3	NP_001291358.1	Q8N292

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPT	ENST00000502276.6	TSL:4 MANE Select	c.250G>A	p.Val84Ile	missense	Exon 3 of 3	ENSP00000423113.2	Q8N292
	GAPT	ENST00000318469.2	TSL:6	c.250G>A	p.Val84Ile	missense	Exon 1 of 1	ENSP00000323075.2	Q8N292
	GAPT	ENST00000396776.6	TSL:2	c.250G>A	p.Val84Ile	missense	Exon 3 of 3	ENSP00000379997.2	Q8N292

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250504 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.1
DANN	Benign	0.39
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.052
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.039
Sift	Benign	0.11	T
Sift4G	Benign	0.36	T
Polyphen		0.0020	B
Vest4		0.048
MutPred		0.079		Gain of helix (P = 0.062)
MVP		0.088
MPC		0.12
ClinPred		0.053	T
GERP RS		-1.6
Varity_R		0.032
gMVP		0.076
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs772963136; hg19: chr5-57790613; COSMIC: COSV108101973; COSMIC: COSV108101973;